Acetylsalicylate of sodium.



\NI'TED STAT -s Patented October 6, 1903.

PATENT OFFICE.

BRUNO RICHARD SEIFERT AND FRIEDRICH RUDOLF ENGELHARDT, OF

RADEBEUL, GERMANY, ASSIGNORS TO CHEMISCHE FABRIK VON HEY- DEN, AOTIENGESELLSOHAFT, OF RADEBEUL, NEAR DRESDEN, SAXONY,

GERMANY.

SPECIFICATION forming part of Letters fatent No. 740,702, dated October 6, 1903.

Application filed June 7, 1902. Serial No. 110,629. (llo specimens.)

To aZZ whom it may concern.-

Be itknown that we, BRUNO RIonAnn Sax- This invention relates to a new and useful I substance for medical purposes, which 'sulo-' stance consists of acetylsalicylate of sodium. According to Kraut in the Annalen 150,

pages 9 to 12, acetylsalicylic acid of the formula O H OO HQOOH is obtained by heatmeans, such as acetyl chlorid or acetanhydrid.

In the United States Letters Patent No.

644,077, dated February 27, 1900, it is sug-,

gested that the Kraut substance be not the real acetylsalicylic acid, but another compound, because Kraut does not state the true point of solidification; but, as a fact, it is to be stated that if worked according to Krauts statement the real acetylsalicylic acid is obtained, such substance being the same as that claimed as a new one in the above-cited United States patent. The statement of a wrong point of solidification in the Annals n, most probably be a clerical error or misprint, and such statement must, furthermore, originate in this, that Krauts statement of the point of solidification has not been established on a pure product. The fact isthat Kraut has recrystallized his acetylsalicylic acid out of boiling water, believing that this could be done without prejudice. As a matter of fact, however, the acetylsalicylic acid is split up by boiling water partly into acetic acid and salicylic acid. Krauts point of solidification therefore does not refer to-pure acetylsalicylic acid, but to an acetylsalicylic acid contaminated with salicylic acid. The melting-point and the point of solidification of acetylsalicylic acid will be considerably reduced by the slightest contamination. The low point of solidification of Kraut is due to this, as well as to the impurity of the salicylic acid of that time. Krauts statement that his acetylsalicylic 5o acid on addition of Fe Ol (ferric chlorid) ing the salicylic acid with an acetylizingwould yield the same violet color as the salicylic acid also refers to the product recrystallized out of water, and consequently contaminated with salicylic acid, for the acetylsalicylic acid obtained according to Krauts statement,but not recrystallized out of Water, does not yield a violet color on addition of Fe OI If salicylic acid is acetylized exactly according to the prescription given by Kraut in the Annalen 150, page 10, it will become neces sary only to wash the raw product with cold water or alcohol or other or benzene in order to directly obtain acetylsalicylic acid which does not deliver the reaction of ferric chlorid on salicylic acid and which melts at 135 centigrade. This substance if used as a medicament has the same effect as the salicylic acid, as the latter will separate from the substance within the human body. It is, however, known that free salicylic acid acts rather strongly irritating. The salicylic acid even keratinizes the skin, and therefore one uses as an internal medicine the salicylate of sodium instead of salicylic acid when large doses are necessary. The acetylsalicylic acid is likewise to be taken only in small doses.

Now we have produced according to our present invention an acetylsalicylate of sodium which has no acid reaction, and therefore no irritating effect. This substance was hitherto not accessible, at least not as a solid substance. Kraut mentions in the An'nalen 150, page 11, that the acetylsalicylic acid will decompose carbonates and that by newtralizing an aqueous solution of soda with acetylsalicylic acid an aqueous solution of acetylsalicylate of sodium is obtained; but this aqueous solution does not permit the ob taining of asolid salt. On evaporation, even 0 in uacuo, decomposition takes place.

We have already mentioned above that the acctylsalicylic acid will become split up into salicylic acid and acetic acid by boiling it with water. This splitting up will take place 5 still more easily in the presence of alkali. By neutralizing acetylsalicylic acid with a solution of sodium carbonate only an aqua one solution of the sodium salt of the acetylsalicylic acid is obtainable, but no solid salt. xoo

ml A.

Kraut has not been able to get a solid salt, for his solution became decomposed by evaporation. Now, taking a new way, we have succeeded in obtaining the acetylsalicylate of sodium in the form of a solid salt. We dissolve or suspend the acetylsalicylic acid not in water, like Kraut, but in one of the following liquids, to wit: alcohols, acetones, ether, bisulfid of carbon, chloroform, carbonyl tetra chlorid, acetic ether, or hydrocarbons, and add to such liquid an alcoholic solution of equivalent quantities of caustic soda or of sodium alcoholate. Thus in contrast with Kraut we avoid water when neutralizing acetylsalicylic acid and use anhydrous solvents, and thus we obtain direct solid sodium salt of acetylsalicylic acid.

According to the quantity and quality of the solvents employed the acetylsalicylate of sodium will precipitatein solid form either immediately or after further addition ofether. The solid salt is separated by filtration, washed, and dried, or if it still shows an alkaline reaction it may be purified by being dissolved or suspended in an alcohol and by being again precipitated with ether.

Example: One part of acetylsalicylic acid is dissolved in thirty parts of ether or suspended in ten parts of ether and afterward neutralized by addition of equivalent quantitiesof an alcoholic soda-lye. In both cases, still before the whole soda-lye is added, the formation of a white crystal magma of acetylsalicylate of sodium will take place, which after being filtered is washed with ether and afterward dried. In correct working a product is obtainedwhich if dissolved in water and mixed with ferric chlorid will not show the reaction of salicylic acid; otherwise the product must be dissolved in alcohol or must be mixed up with alcohol to form a magma and must afterward again be precipitated by ether.

The acetylsalicylate of sodium in solid form is a newtechnical product hitherto unknown, which does not ofier any inconvenience to the trade, while Krauts aqueous solution was little suitable for commercial purposes and for consumption, its liquid form and disposition to decompose rendering conveyance and application very diflicult. The new salt is an odorless powder having a weak salty taste, contrary to the disagreeable sweet taste of salicylate of sodium. It has neutral reaction, is free of the irritating efiects of the acetylsalicylic acid, insoluble in ether and benzene, but most easily soluble in cold water. The aqueous solution of the same will on addition of ferric chlorid yield no violet color as the salicylic acid does, but a flesh-colored precipitate of acetylsalicylate of iron. If hydrochloric acid is added to the aqueous solution, the acetylsalicylic acid of the melting-point 135 centigrade will be precipitated.

What we claim as our invention is- The new product herein described consisting of solid acetylsalicylate of sodium, having the formula 6 coona.

forming a white powder of neutral reaction, free from the intensive taste of salicylate of sodium having merely a slightly salty taste, insoluble in ether and benzene, highly soluble in cold water, yielding in watery solution no violet color on addition of ferric chlorid, and yielding acetylsalicylic acid of 135 centi grade melting-point on addition of hydro chloric acid.

In testimony that we claim the foregoing as our invention we have signed our names, in presence of two witnesses, this 24th day of May, 1902.

BRUNO RICHARD SEIFERT. FRIEDRICH RUDOLF ENGELHARDT. Witnesses:

PAUL E. SOHILLING, HERNANDQ DE SoTo. 

